Background: Correlations between bone marrow, heart, kidney, liver, skin and lung transplant rejection or survival with human cytokine gene polymorphisms have been described. There are also reports about the role of cytokines and Tumor Necrosis Factors-Alpha (TNF-α) on corneal transplant in animal models. Further studies are needed to clarify the role of cytokines in corneal allograft rejection in humans. Objective: To study whether corneal allograft rejection is associated with TNF-α gene polymorphism. Methods: A total of 105 cases of corneal transplant were followed for a mean period of 25.9 months and the episodes of rejections recorded. We determined allele-specific PCR (ASPCR) TNF-α gene polymorphism of the patients and evaluated their association with rejection. Results: The overall incidence of corneal graft rejection and its subsequent recovery were 21% and 63.6% respectively. Rejection was more common in the vascularized corneas (5.4 folds; P<0.001), and in eyes with anterior synechia (3.9 fold; P<0.05). There was no correlation between TNF-α gene polymorphism and the chance of allograft rejection. Conclusion: No association was found between human TNF-α-308 G/A promoter gene polymorphism and corneal allograft rejection in our cases of uncomplicated penetrating keratoplasty.